MSC2015103B in Solid Tumors
Sponsor
EMD Serono (Industry)
Overall Status
Terminated
CT.gov ID
NCT01453387
Collaborator
(none)
28
3
2
22
9.3
0.4
Study Details
Study Description
Brief Summary
The main purpose of this study is to test the experimental drug, MSC2015103B at different dose levels and on different treatment schedules, to see whether it is safe and can be tolerated when given to subjects once a day one day per week over a 21-day period or once a day three times per week over a 21-day period. The investigators would also like to find out how MSC2015103B is broken down by the body.
Additional purposes of the trial are to assess side effects of MSC2015103B and to find out whether MSC2015103B has anti-cancer effects. In addition, the investigators would like to explore pharmacokinetics.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
28 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Dose-Escalation First-In-Human Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral MEK Inhibitor MSC2015103B Administered With Two Different Treatment Schedules in Subjects With Advanced Solid Tumors
Study Start Date
:
Sep 1, 2011
Actual Primary Completion Date
:
Jul 1, 2013
Actual Study Completion Date
:
Jul 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 - MSC2015103B (Schedule 1)
|
Drug: MSC2015103B
Schedule 1: MSC2015103B will be administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD establishment. Starting dose will be 150 microgram (mcg), which will be escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently.
|
| Experimental: Part 1 - MSC2015103B (Schedule 2)
|
Drug: MSC2015103B
Schedule 2: MSC2015103B will be administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose will be 150 mcg, and will be escalated to 200 mcg subsequently.
|
Outcome Measures
Primary Outcome Measures
- Number of Subjects Who Experienced Dose-limiting Toxicities (DLT) [Up to Day 21 of Cycle 1]
DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to progressive disease (PD) at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.
- Percentage of Subjects Who Experienced DLT [Up to Day 21 of Cycle 1]
DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to PD at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition.
Secondary Outcome Measures
- Percentage of Subjects Who Experienced Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation [From the initiation of the trial till the data cut-off date 15 July 2013]
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. SAE (Serious adverse event) is defined as any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.. TEAEs are events between first dose of study drug up to the cut-off date (15 July 2013) and were absent before treatment or that worsened relative to pretreatment state.
- Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication [From the initiation of the trial till the data cut-off date 15 July 2013]
Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs.
- Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication [From the initiation of the trial till the data cut-off date 15 July 2013]
Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs.
- Maximum Plasma Concentration (Cmax) [Schedule 1 : 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Days 1 and 17.]
- Time to Reach Maximum Plasma Concentration (Tmax) [Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.]
- Apparent Terminal Half Life (T1/2) [Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.]
The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination.
- Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-inf]) [Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.]
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
- AUC Versus Time Curve Within One Dosing Interval (AUC0-tau) [Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17.]
- Apparent Oral Clearance of the Drug From Plasma (CL/f) [Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1.]
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed.
- Apparent Volume of Distribution Associated to the Terminal Phase (Vz/f) [Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1.]
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.
- Extracellular Signal-regulated Kinase (ERK) Phosphorylation Levels [Schedule 1: Day 1: Pre-dose; Post-dose: 2, 4, 8, 24 hour; 48 or 72 hour; 48 or 96 hour, 168 hour; Day 15: Pre-dose; Schedule 2: Day 1: Pre-dose; Post-dose: 2, 8, 24, 48, 96 hour; Day 15: Pre-dose; Day 17: Pre-dose; Post-dose: 2, 8, and 24 hour]
ERK phosphorylation levels were to be assessed in peripheral blood mononuclear cells (PBMC) during the dose escalation
- Percentage of Subjects With Overall Response [Every 6 Weeks until complete response or till data cut-off date 15 July 2013]
Overall response was to be confirmed by complete response (CR) or partial response (PR) using response evaluation criteria in solid tumours Version 1.0 (RECIST) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline.
- Percentage of Subjects With Clinical Benefit [Every 6 Weeks until complete response or till data cut-off date 15 July 2013]
Clinical benefit was to be confirmed by CR, PR or stable disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Pathologically confirmed solid tumor preferably, but not exclusively, including pancreatic, thyroid, colorectal, non-small cell lung, endometrial, renal, breast, ovarian carcinoma, or melanoma which is locally advanced or metastatic, and either refractory after standard therapy for the disease or for which no effective standard therapy is available
-
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (<=) 1
-
Has read and understands the informed consent form and is willing and able to give informed consent. Fully understands requirements of and willing to comply with all trial visits and assessments
-
Evidence of measurable disease at trial entry as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.0.
-
Willing to provide archival tissue samples for molecular analysis
Other inclusion criteria as defined in protocol.
Exclusion Criteria
-
Bone marrow impairment as evidenced by hemoglobin less than (<) 9.0 gram per deciliter (g/dL), neutrophil count < 1.5 x 109 per liter (/L), and/or platelets <100 x 109/L per liter (/L)
-
Renal impairment as evidenced by serum creatinine greater than (>) 1.5 x upper limit of normal (ULN) and/or calculated creatinine clearance < 50 milliliter per minute (mL/min) (Cockcroft-Gault formula)
-
Liver function and liver cell integrity abnormality as defined by total bilirubin > 1.5 x ULN, or aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 2.5 x ULN, for subjects with liver involvement AST/ALT > 5 x ULN. Subjects with albumin < 2.5 g/dL are also excluded
-
History of central nervous system (CNS) metastases.
-
History of difficulty of swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the tested product.
-
Chronic diarrhea that is >= Grade 2 in severity
-
Clinically significant cardiac conduction abnormalities
-
A left ventricular ejection fraction of < 45%
-
A history of stroke or myocardial infarction within the past year
-
A history of uveitis and scleritis
-
Retinal pathology beyond normal age-related processes
-
Evidence of a retinal vein occlusion on fluorescein angiogram or a history of retinal vein occlusion
-
Subjects are also excluded if their ophthalmologist finds that their optic disc is at risk for a central retinal vein occlusion
-
History of glaucoma
-
Subjects requiring daily and/or chronic systemic steroids
-
Pregnant or nursing females Other exclusion criteria as defined in protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | |
| 2 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | |
| 3 | Karmanos Cancer Institute | Detroit | Michigan | United States |
Sponsors and Collaborators
- EMD Serono
Investigators
- Study Director: Medical Responsible, Merck Serono, a division of Merck KGaA, Darmstadt, Germany
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
EMD Serono
ClinicalTrials.gov Identifier:
NCT01453387
Other Study ID Numbers:
- EMR 200064-001
First Posted:
Oct 17, 2011
Last Update Posted:
May 8, 2017
Last Verified:
Mar 1, 2017
Keywords provided by EMD Serono
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | First/Last subject (informed consent): 09 September 2011/18 April 2013. Study completion date: 15 July 2013, Clinical data cut-off date: 15 July 2013; Subjects were randomized at 3 centers in United States. |
|---|---|
| Pre-assignment Detail | Enrolled: 28 subjects were screened for eligibility and all were randomized in to the trial. |
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently. |
| Period Title: Overall Study | ||
| STARTED | 21 | 7 |
| COMPLETED | 21 | 7 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) | Total |
|---|---|---|---|
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently. | Total of all reporting groups |
| Overall Participants | 21 | 7 | 28 |
| Age, Customized (Subjects) [Number] | |||
| 18 to less than (<) 45 years |
2
|
0
|
2
|
| Greater than equal to (>=) 45 to <65 years |
10
|
5
|
15
|
| >=65 years |
9
|
2
|
11
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
4
19%
|
4
57.1%
|
8
28.6%
|
| Male |
17
81%
|
3
42.9%
|
20
71.4%
|
Outcome Measures
| Title | Number of Subjects Who Experienced Dose-limiting Toxicities (DLT) |
|---|---|
| Description | DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to progressive disease (PD) at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition. |
| Time Frame | Up to Day 21 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all the subjects who received at least one administration of the trial medication. |
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until maximum tolerated dose (MTD) was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently. |
| Measure Participants | 21 | 7 |
| Number [Subjects] |
0
|
0
|
| Title | Percentage of Subjects Who Experienced DLT |
|---|---|
| Description | DLT was evaluated using the National cancer institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLT was defined as any of the following AEs occurring during Cycle 1 that are not related to PD at any dose level: Any Grade 3 or more non-hematological toxicity excluding: Grade 3 diarrhea or associated electrolyte abnormalities that were controlled with adequate and optimal therapies, Grade 3 liver function abnormalities which resolved within 7 days, vomiting. Grade 4 neutropenia of greater than (>) 5 days duration or Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, any severe or life threatening AE or any AE or abnormality which impairs daily normal physiological functions, any treatment delay for 2 weeks or more due to adverse effects not related to PD. All events judged to be related by the Investigator to PD were excluded from the DLT definition. |
| Time Frame | Up to Day 21 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all subjects who received at least one administration of the trial medication. |
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently. |
| Measure Participants | 21 | 7 |
| Number [Percentage of subjects] |
0
|
0
|
| Title | Percentage of Subjects Who Experienced Any Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation |
|---|---|
| Description | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. SAE (Serious adverse event) is defined as any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.. TEAEs are events between first dose of study drug up to the cut-off date (15 July 2013) and were absent before treatment or that worsened relative to pretreatment state. |
| Time Frame | From the initiation of the trial till the data cut-off date 15 July 2013 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all the subjects who received at least one administration of the trial medication. |
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently. |
| Measure Participants | 21 | 7 |
| TEAEs |
100.0
|
100.0
|
| Serious TEAEs |
19.0
|
42.9
|
| TEAEs leading to death |
0.0
|
0.0
|
| TEAEs leading to discontinuation |
0.0
|
14.3
|
| Title | Percentage of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication |
|---|---|
| Description | Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs. |
| Time Frame | From the initiation of the trial till the data cut-off date 15 July 2013 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all the subjects who received at least one administration of the trial medication. |
| Arm/Group Title | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | The planned dose of MSC2015103B (150 mcg, 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg) was orally administered once weekly on Days 1, 8, and 15 of a 21-day cycle. | The planned dose of MSC2015103B (150 mcg and 200 mcg) was orally administered thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 21 | 7 |
| Aspartate aminotransferase increased |
14.3
|
0.0
|
| Decreased appetite |
14.3
|
14.3
|
| Gamma-glutamyl transferase increased |
0.0
|
14.3
|
| Blood alkaline phosphatase increased |
0.0
|
14.3
|
| Ejection fraction decreased |
0.0
|
14.3
|
| Blood glucose increased |
0.0
|
14.3
|
| Hypokalemia |
0.0
|
28.6
|
| Hyponatraemia |
0.0
|
28.6
|
| Hypoalbuminaemia |
0.0
|
14.3
|
| Hypophosphatemia |
0.0
|
14.3
|
| Title | Number of Subjects Who Experienced Clinically Significant Lab Abnormality Judged to be Related to the Trial Medication |
|---|---|
| Description | Abnormal laboratory findings and other abnormal investigational findings which were associated with clinical signs and symptoms, lead to treatment discontinuation, or considered medically important by the investigator were reported as AEs. |
| Time Frame | From the initiation of the trial till the data cut-off date 15 July 2013 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all the subjects who received at least one administration of the trial medication. |
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | The planned dose of MSC2015103B (150 mcg, 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg) was orally administered once weekly on Days 1, 8, and 15 of a 21-day cycle. | The planned dose of MSC2015103B (150 mcg and 200 mcg) was orally administered thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 21 | 7 |
| Aspartate aminotransferase increased |
3
|
0
|
| Decreased appetite |
3
|
1
|
| Gamma-glutamyl transferase increased |
0
|
1
|
| Blood alkaline phosphatase increased |
0
|
1
|
| Ejection fraction decreased |
0
|
1
|
| Blood glucose increased |
0
|
1
|
| Hypokalemia |
0
|
2
|
| Hyponatraemia |
0
|
2
|
| Hypoalbuminaemia |
0
|
1
|
| Hypophosphatemia |
0
|
1
|
| Title | Maximum Plasma Concentration (Cmax) |
|---|---|
| Description | |
| Time Frame | Schedule 1 : 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Days 1 and 17. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set included all the subjects who received at least 1 dose of MSC2015103B and provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "n" signifies the number of subjects evaluable for the particular timepoint. |
| Arm/Group Title | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MSC2015103B 150 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 3 | 4 | 3 | 3 | 3 | 3 | 2 | 3 | 4 |
| Week 1 (n=3, 4, 3, 3, 3, 3, 2, 3, 4) |
38.750
|
38.110
|
97.293
|
290.98
|
396.45
|
888.15
|
2215.9
|
75.313
|
52.331
|
| Week 2 (n= 3,3,3,3,1,3,2,2,3) |
48.952
|
63.732
|
219.71
|
329.62
|
2471.0
|
1728.1
|
5636.8
|
190.59
|
157.62
|
| Title | Time to Reach Maximum Plasma Concentration (Tmax) |
|---|---|
| Description | |
| Time Frame | Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set included all the subjects who received at least 1 dose of MSC2015103B and provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "n" signifies the number of subjects evaluable for the particular timepoint. |
| Arm/Group Title | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MSC2015103B 150 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 3 | 4 | 3 | 3 | 3 | 3 | 2 | 3 | 4 |
| Week 1 (n=3,4,3,3,3,3,2,3,4) |
2.4478
|
5.2643
|
1.4422
|
1.4422
|
1.5874
|
1.1447
|
1.2450
|
2.4248
|
1.3161
|
| Week 3 (n=3,3,3,3,1,3,2,2,3) |
1.1573
|
2.3833
|
4.5789
|
1.1635
|
0.50000
|
2.0110
|
0.70711
|
2.8519
|
1.6869
|
| Title | Apparent Terminal Half Life (T1/2) |
|---|---|
| Description | The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. |
| Time Frame | Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set included all the subjects who received at least 1 dose of MSC2015103B and provided sufficient plasma concentrations of MSC2015103B measurement after the first dose."n" signifies the number of subjects evaluable for the particular timepoint. |
| Arm/Group Title | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MSC2015103B 150 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. | MSC2015103B 200 mcg was orally administered thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 3 | 4 | 3 | 3 | 3 | 3 | 2 | 3 | 4 |
| Week 1 (n=3,4,3,3,3,3,2,3,4) |
134.88
|
115.41
|
55.023
|
53.072
|
115.34
|
52.852
|
81.124
|
30.850
|
33.007
|
| Week 3 (n=3,3,3,3,1,3,2,2,3) |
102.30
|
102.53
|
138.47
|
55.43
|
37.16
|
103.77
|
100.91
|
121.58
|
145.70
|
| Title | Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-inf]) |
|---|---|
| Description | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. |
| Time Frame | Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set included all the subjects who have received at least 1 dose of MSC2015103B and provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "n" signifies the number of subjects evaluable for the particular timepoint. |
| Arm/Group Title | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MSC2015103B 150 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. | MSC2015103B 200 mcg was orally administered thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 3 | 4 | 3 | 3 | 3 | 3 | 2 | 3 | 4 |
| Week 1 (n=3,4,3,3,3,3,2,3,4) |
3644.7
|
3927.4
|
2249.9
|
7890.1
|
12454
|
13164
|
23558
|
2032.2
|
1375.2
|
| Week 3 (n=,3,3,3,3,1,3,2,2,3) |
4715.2
|
4377.2
|
16465
|
12397
|
24580
|
35423
|
66081
|
21735
|
14870
|
| Title | AUC Versus Time Curve Within One Dosing Interval (AUC0-tau) |
|---|---|
| Description | |
| Time Frame | Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1 and Week 3; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1 and 17. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set included all the subjects who received at least 1 dose of MSC2015103B and provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "n" signifies the number of subjects evaluable for the particular timepoint. |
| Arm/Group Title | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MSC2015103B 150 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. | MSC2015103B 200 mcg was orally administered thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 3 | 4 | 3 | 3 | 3 | 3 | 2 | 3 | 4 |
| Week 1 (n=3,4,3,3,3,3,2,3,4) |
2072.8
|
2381.6
|
1752.7
|
6824.4
|
8434.6
|
11533
|
17698
|
1345.3
|
865.76
|
| Week 3 (n=3,3,3,3,1,3,2,2,3) |
2946.9
|
3002.0
|
8865.3
|
10696
|
23670
|
25150
|
47114
|
4993.3
|
3070.5
|
| Title | Apparent Oral Clearance of the Drug From Plasma (CL/f) |
|---|---|
| Description | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/f was influenced by the fraction absorbed. |
| Time Frame | Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set included all the subjects who have received at least one dose of MSC2015103B and who have provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "N" signifies the total number of subjects evaluable for this outcome measure. |
| Arm/Group Title | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MSC2015103B 150 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 150 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 3 | 4 | 3 | 3 | 3 | 3 | 2 | 3 | 4 |
| Geometric Mean (Full Range) [Liter/hour] |
41.156
|
50.924
|
133.34
|
57.033
|
52.192
|
75.968
|
63.673
|
73.813
|
145.44
|
| Title | Apparent Volume of Distribution Associated to the Terminal Phase (Vz/f) |
|---|---|
| Description | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. |
| Time Frame | Schedule 1: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0, 48 or 72, 72 or 96 and 168 hours post-dose during Week 1; Schedule 2: 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, and 24.0 hours post-dose on Day 1. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set included all the subjects who received at least 1 dose of MSC2015103B and who provided sufficient plasma concentrations of MSC2015103B measurement after the first dose. "n" signifies the number of subjects evaluable for the particular timepoint. |
| Arm/Group Title | Part 1 - MSC2015103B 150 mcg (Schedule 1) | Part 1 - MSC2015103B 200 mcg (Schedule 1) | Part 1 - MSC2015103B 300 mcg (Schedule 1) | Part 1 - MSC2015103B 450 mcg (Schedule 1) | Part 1 - MSC2015103B 650 mcg (Schedule 1) | Part 1 - MSC2015103B 1000 mcg (Schedule 1) | Part 1 - MSC2015103B 1500 mcg (Schedule 1) | Part 1 - MSC2015103B 150 mcg (Schedule 2) | Part 1 - MSC2015103B 200 mcg (Schedule 2) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MSC2015103B 150 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 300 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 450 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 650 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1000 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 1500 mcg was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle. | MSC2015103B 150 mcg was orally administered thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. | MSC2015103B 200 mcg was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle. |
| Measure Participants | 3 | 4 | 3 | 3 | 3 | 3 | 2 | 3 | 4 |
| Geometric Mean (Full Range) [Liter] |
8008.6
|
8478.7
|
10584
|
4366.9
|
8684.7
|
5792.4
|
7452.2
|
3285.2
|
6925.6
|
| Title | Extracellular Signal-regulated Kinase (ERK) Phosphorylation Levels |
|---|---|
| Description | ERK phosphorylation levels were to be assessed in peripheral blood mononuclear cells (PBMC) during the dose escalation |
| Time Frame | Schedule 1: Day 1: Pre-dose; Post-dose: 2, 4, 8, 24 hour; 48 or 72 hour; 48 or 96 hour, 168 hour; Day 15: Pre-dose; Schedule 2: Day 1: Pre-dose; Post-dose: 2, 8, 24, 48, 96 hour; Day 15: Pre-dose; Day 17: Pre-dose; Post-dose: 2, 8, and 24 hour |
Outcome Measure Data
| Analysis Population Description |
|---|
| As the trial was terminated early due to administrative reason, it was decided as per Statistical Analysis Plan not to evaluate the biomarker data for this study. |
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, which was escalated to 200 mcg. |
| Measure Participants | 0 | 0 |
| Title | Percentage of Subjects With Overall Response |
|---|---|
| Description | Overall response was to be confirmed by complete response (CR) or partial response (PR) using response evaluation criteria in solid tumours Version 1.0 (RECIST) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline. |
| Time Frame | Every 6 Weeks until complete response or till data cut-off date 15 July 2013 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The efficacy analysis set included all subjects who received at least 1(non-zero) dose of MSC2015103B and had a baseline tumor assessment. |
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, which was escalated to 200 mcg. |
| Measure Participants | 21 | 7 |
| CR |
0
|
0
|
| PR |
0
|
0
|
| Title | Percentage of Subjects With Clinical Benefit |
|---|---|
| Description | Clinical benefit was to be confirmed by CR, PR or stable disease (SD) lasting at least 6 weeks (using RECIST v1.0) during treatment. CR: The disappearance of all target and non-target lesions and normalization of tumor marker level; PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started. |
| Time Frame | Every 6 Weeks until complete response or till data cut-off date 15 July 2013 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The efficacy analysis set included all subjects who received at least 1(non-zero) dose of MSC2015103B and had a baseline tumor assessment. |
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) |
|---|---|---|
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, which was escalated to 200 mcg. |
| Measure Participants | 21 | 7 |
| Number [percentage of subjects] |
33.3
|
28.6
|
Adverse Events
| Time Frame | From the initiation of the trial till data cut-off date (15 July 2013) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) | ||
| Arm/Group Description | MSC2015103B was administered orally once weekly on Days 1, 8, and 15 of a 21-day cycle until MTD was established. Starting dose was 150 microgram (mcg), which was escalated to 200 mcg, 300 mcg, 450 mcg, 650 mcg, 1000 mcg and 1500 mcg subsequently. | MSC2015103B was administered orally thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17 and 19 of a 21-day cycle until MTD was established. Starting dose was 150 mcg, and was escalated to 200 mcg subsequently. | ||
All Cause Mortality |
||||
| Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/21 (19%) | 3/7 (42.9%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Nausea | 0/21 (0%) | 1/7 (14.3%) | ||
| Vomiting | 0/21 (0%) | 1/7 (14.3%) | ||
| Infections and infestations | ||||
| Pneumonia | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Septic shock | 1/21 (4.8%) | 0/7 (0%) | ||
| Catheter site infection | 0/21 (0%) | 1/7 (14.3%) | ||
| Injury, poisoning and procedural complications | ||||
| Feeding tube complication | 0/21 (0%) | 1/7 (14.3%) | ||
| Metabolism and nutrition disorders | ||||
| Hypokalaemia | 1/21 (4.8%) | 0/7 (0%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 1/21 (4.8%) | 0/7 (0%) | ||
| Nephrolithiasis | 1/21 (4.8%) | 0/7 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 1/21 (4.8%) | 0/7 (0%) | ||
| Haemoptysis | 1/21 (4.8%) | 0/7 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Part 1 - MSC2015103B (Schedule 1) | Part 1 - MSC2015103B (Schedule 2) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 21/21 (100%) | 7/7 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 4/21 (19%) | 1/7 (14.3%) | ||
| Iron deficiency anaemia | 3/21 (14.3%) | 0/7 (0%) | ||
| Lymphadenopathy | 1/21 (4.8%) | 0/7 (0%) | ||
| Thrombocytopenia | 1/21 (4.8%) | 0/7 (0%) | ||
| Leukopenia | 0/21 (0%) | 1/7 (14.3%) | ||
| Neutropenia | 0/21 (0%) | 1/7 (14.3%) | ||
| Cardiac disorders | ||||
| Bradycardia | 1/21 (4.8%) | 0/7 (0%) | ||
| Palpitations | 1/21 (4.8%) | 0/7 (0%) | ||
| Sinus tachycardia | 1/21 (4.8%) | 0/7 (0%) | ||
| Aortic valve incompetence | 0/21 (0%) | 1/7 (14.3%) | ||
| Aortic valve sclerosis | 0/21 (0%) | 1/7 (14.3%) | ||
| Tachycardia | 0/21 (0%) | 1/7 (14.3%) | ||
| Eye disorders | ||||
| Scleral haemorrhage | 1/21 (4.8%) | 0/7 (0%) | ||
| Eyelid ptosis | 0/21 (0%) | 1/7 (14.3%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 5/21 (23.8%) | 1/7 (14.3%) | ||
| Abdominal pain upper | 2/21 (9.5%) | 1/7 (14.3%) | ||
| Constipation | 1/21 (4.8%) | 3/7 (42.9%) | ||
| Dental caries | 1/21 (4.8%) | 0/7 (0%) | ||
| Diarrhoea | 6/21 (28.6%) | 0/7 (0%) | ||
| Dry mouth | 1/21 (4.8%) | 0/7 (0%) | ||
| Gastrooesophageal reflux disease | 1/21 (4.8%) | 0/7 (0%) | ||
| Gingival pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Nausea | 3/21 (14.3%) | 3/7 (42.9%) | ||
| Retching | 2/21 (9.5%) | 0/7 (0%) | ||
| Stomatitis | 2/21 (9.5%) | 1/7 (14.3%) | ||
| Vomiting | 3/21 (14.3%) | 1/7 (14.3%) | ||
| Abdominal tenderness | 0/21 (0%) | 1/7 (14.3%) | ||
| Frequent bowel movements | 0/21 (0%) | 1/7 (14.3%) | ||
| General disorders | ||||
| Asthenia | 1/21 (4.8%) | 0/7 (0%) | ||
| Axillary pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Breakthrough pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Chest pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Early satiety | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Fatigue | 9/21 (42.9%) | 2/7 (28.6%) | ||
| Influenza like illness | 1/21 (4.8%) | 1/7 (14.3%) | ||
| oedema | 1/21 (4.8%) | 0/7 (0%) | ||
| Oedema peripheral | 3/21 (14.3%) | 1/7 (14.3%) | ||
| Pyrexia | 1/21 (4.8%) | 2/7 (28.6%) | ||
| Device occlusion | 0/21 (0%) | 1/7 (14.3%) | ||
| Gait disturbance | 0/21 (0%) | 1/7 (14.3%) | ||
| Suprapubic pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Thirst | 1/21 (4.8%) | 0/7 (0%) | ||
| Hepatobiliary disorders | ||||
| Bile duct obstruction | 1/21 (4.8%) | 0/7 (0%) | ||
| Immune system disorders | ||||
| Seasonal allergy | 1/21 (4.8%) | 0/7 (0%) | ||
| Infections and infestations | ||||
| Bronchitis | 1/21 (4.8%) | 0/7 (0%) | ||
| Laryngitis | 1/21 (4.8%) | 0/7 (0%) | ||
| Nasopharyngitis | 1/21 (4.8%) | 0/7 (0%) | ||
| Sepsis | 1/21 (4.8%) | 0/7 (0%) | ||
| Tooth infection | 1/21 (4.8%) | 0/7 (0%) | ||
| Tracheobronchitis | 1/21 (4.8%) | 0/7 (0%) | ||
| Upper respiratory tract infection | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Catheter site infection | 0/21 (0%) | 1/7 (14.3%) | ||
| Urinary tract infection | 1/21 (4.8%) | 2/7 (28.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Arthropod bite | 1/21 (4.8%) | 0/7 (0%) | ||
| Overdose | 1/21 (4.8%) | 0/7 (0%) | ||
| Post procedural haemorrhage | 1/21 (4.8%) | 0/7 (0%) | ||
| Thermal burn | 1/21 (4.8%) | 0/7 (0%) | ||
| Excoriation | 0/21 (0%) | 1/7 (14.3%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/21 (4.8%) | 0/7 (0%) | ||
| Aspartate aminotransferase increased | 6/21 (28.6%) | 0/7 (0%) | ||
| Blood alkaline phosphatase increased | 4/21 (19%) | 1/7 (14.3%) | ||
| Blood creatinine increased | 1/21 (4.8%) | 0/7 (0%) | ||
| Blood phosphorus decreased | 1/21 (4.8%) | 0/7 (0%) | ||
| Brain natriuretic peptide increased | 1/21 (4.8%) | 0/7 (0%) | ||
| Breathe sounds abnormal | 1/21 (4.8%) | 0/7 (0%) | ||
| Ejection fraction decreased | 2/21 (9.5%) | 1/7 (14.3%) | ||
| Gamma-glutamyl transferase increased | 4/21 (19%) | 1/7 (14.3%) | ||
| Haemoglobin decreased | 1/21 (4.8%) | 0/7 (0%) | ||
| International normalised ratio increased | 1/21 (4.8%) | 0/7 (0%) | ||
| Protein total increased | 1/21 (4.8%) | 0/7 (0%) | ||
| Weight increased | 4/21 (19%) | 0/7 (0%) | ||
| Blood glucose increased | 0/21 (0%) | 1/7 (14.3%) | ||
| Electrocardiogram QT prolonged | 0/21 (0%) | 1/7 (14.3%) | ||
| Weight decreased | 0/21 (0%) | 1/7 (14.3%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 6/21 (28.6%) | 1/7 (14.3%) | ||
| Dehydration | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Hyperglycaemia | 2/21 (9.5%) | 0/7 (0%) | ||
| Hyperkalaemia | 2/21 (9.5%) | 0/7 (0%) | ||
| Hypoalbuminaemia | 2/21 (9.5%) | 1/7 (14.3%) | ||
| Hypocalcaemia | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Hypoglycaemia | 1/21 (4.8%) | 0/7 (0%) | ||
| Hypokalaemia | 2/21 (9.5%) | 3/7 (42.9%) | ||
| Hypomagnesaemia | 2/21 (9.5%) | 1/7 (14.3%) | ||
| Hyponatraemia | 1/21 (4.8%) | 3/7 (42.9%) | ||
| Hypophosphataemia | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Malnutrition | 0/21 (0%) | 1/7 (14.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/21 (0%) | 1/7 (14.3%) | ||
| Backpain | 2/21 (9.5%) | 2/7 (28.6%) | ||
| Flank pain | 2/21 (9.5%) | 0/7 (0%) | ||
| Groin pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Musculoskeletal pain | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Muscle spasms | 0/21 (0%) | 1/7 (14.3%) | ||
| Myalgia | 1/21 (4.8%) | 0/7 (0%) | ||
| Pain in extremity | 4/21 (19%) | 0/7 (0%) | ||
| Nervous system disorders | ||||
| Dizziness | 1/21 (4.8%) | 2/7 (28.6%) | ||
| Headache | 2/21 (9.5%) | 1/7 (14.3%) | ||
| Neuropathy peripheral | 0/21 (0%) | 1/7 (14.3%) | ||
| Tremor | 0/21 (0%) | 1/7 (14.3%) | ||
| Psychiatric disorders | ||||
| Anxiety | 2/21 (9.5%) | 0/7 (0%) | ||
| Insomnia | 2/21 (9.5%) | 0/7 (0%) | ||
| Depression | 0/21 (0%) | 1/7 (14.3%) | ||
| Mood altered | 0/21 (0%) | 1/7 (14.3%) | ||
| Renal and urinary disorders | ||||
| Dysuria | 0/21 (0%) | 1/7 (14.3%) | ||
| Proteinuria | 0/21 (0%) | 1/7 (14.3%) | ||
| Urinary incontinence | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Hydronephrosis | 1/21 (4.8%) | 0/7 (0%) | ||
| Hydroureter | 1/21 (4.8%) | 0/7 (0%) | ||
| Nocturia | 1/21 (4.8%) | 0/7 (0%) | ||
| Obstructive uropathy | 1/21 (4.8%) | 0/7 (0%) | ||
| Pollakiuria | 1/21 (4.8%) | 0/7 (0%) | ||
| Renal failure | 1/21 (4.8%) | 0/7 (0%) | ||
| Urinary hesitation | 1/21 (4.8%) | 0/7 (0%) | ||
| Reproductive system and breast disorders | ||||
| Perineal pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 5/21 (23.8%) | 0/7 (0%) | ||
| Dyspnoea | 2/21 (9.5%) | 0/7 (0%) | ||
| Epistaxis | 2/21 (9.5%) | 0/7 (0%) | ||
| Haemoptysis | 1/21 (4.8%) | 0/7 (0%) | ||
| Laryngeal haemorrhage | 1/21 (4.8%) | 0/7 (0%) | ||
| Nasal congestion | 2/21 (9.5%) | 0/7 (0%) | ||
| Oropharyngeal pain | 1/21 (4.8%) | 0/7 (0%) | ||
| Pleural effusion | 1/21 (4.8%) | 1/7 (14.3%) | ||
| Rhinitis allergic | 1/21 (4.8%) | 0/7 (0%) | ||
| Upper-airway cough syndrome | 1/21 (4.8%) | 0/7 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Actinic keratosis | 1/21 (4.8%) | 0/7 (0%) | ||
| Dermatitis acneiform | 4/21 (19%) | 0/7 (0%) | ||
| Dry skin | 1/21 (4.8%) | 0/7 (0%) | ||
| Erythema | 1/21 (4.8%) | 0/7 (0%) | ||
| Hyperhidrosis | 2/21 (9.5%) | 0/7 (0%) | ||
| Night sweats | 1/21 (4.8%) | 0/7 (0%) | ||
| Pruritus | 1/21 (4.8%) | 0/7 (0%) | ||
| Pruritus generalized | 0/21 (0%) | 1/7 (14.3%) | ||
| Skin haemorrhage | 1/21 (4.8%) | 0/7 (0%) | ||
| Skin hypopigmentation | 1/21 (4.8%) | 0/7 (0%) | ||
| Swelling face | 1/21 (4.8%) | 0/7 (0%) | ||
| Surgical and medical procedures | ||||
| Biliary drainage | 0/21 (0%) | 1/7 (14.3%) | ||
| Vascular disorders | ||||
| Hypotension | 1/21 (4.8%) | 0/7 (0%) | ||
| Hypertension | 1/21 (4.8%) | 0/7 (0%) | ||
| Orthostatic hypotension | 1/21 (4.8%) | 1/7 (14.3%) | ||
Limitations/Caveats
The study was terminated early during Part 1 of the trial due to administrative reason. Pharmacodynamics evaluations were not performed due to early termination.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The study as a whole will be published prior to any individual investigator publications. It is required that copies of all papers, abstracts, articles, etc. that contain study data are to be forward to the Sponsor for review 30 days prior to submission for publication.
Results Point of Contact
| Name/Title | Merck KGaA Communication Center |
|---|---|
| Organization | Merck Serono, a division of Merck KGaA |
| Phone | +49-6151-72-5200 |
| service@merckgroup.com |
Responsible Party:
EMD Serono
ClinicalTrials.gov Identifier:
NCT01453387
Other Study ID Numbers:
- EMR 200064-001
First Posted:
Oct 17, 2011
Last Update Posted:
May 8, 2017
Last Verified:
Mar 1, 2017